Human pallial MGE-type GABAergic interneuron cell therapy for chronic focal epilepsy

Cell Stem Cell. 2023 Oct 5;30(10):1331-1350.e11. doi: 10.1016/j.stem.2023.08.013.


Mesial temporal lobe epilepsy (MTLE) is the most common focal epilepsy. One-third of patients have drug-refractory seizures and are left with suboptimal therapeutic options such as brain tissue-destructive surgery. Here, we report the development and characterization of a cell therapy alternative for drug-resistant MTLE, which is derived from a human embryonic stem cell line and comprises cryopreserved, post-mitotic, medial ganglionic eminence (MGE) pallial-type GABAergic interneurons. Single-dose intrahippocampal delivery of the interneurons in a mouse model of chronic MTLE resulted in consistent mesiotemporal seizure suppression, with most animals becoming seizure-free and surviving longer. The grafted interneurons dispersed locally, functionally integrated, persisted long term, and significantly reduced dentate granule cell dispersion, a pathological hallmark of MTLE. These disease-modifying effects were dose-dependent, with a broad therapeutic range. No adverse effects were observed. These findings support an ongoing phase 1/2 clinical trial (NCT05135091) for drug-resistant MTLE.

Keywords: GABA; MGE; TLE; cell therapy; epilepsy; hESC; interneuron; seizure; transplant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / pathology
  • Epilepsy, Temporal Lobe* / pathology
  • Epilepsy, Temporal Lobe* / surgery
  • Hippocampus* / pathology
  • Humans
  • Interneurons / physiology
  • Mice
  • Seizures / pathology
  • Seizures / surgery

Associated data